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1.
BMJ Open ; 14(4): e082764, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38604630

RESUMO

INTRODUCTION: Poststroke cognitive impairment is a common complication in stroke survivors, seriously affecting their quality of life. Therefore, it is crucial to improve cognitive function of patients who had a stroke. Transcranial direct current stimulation (tDCS) and transcutaneous auricular vagus nerve stimulation (taVNS) are non-invasive, safe treatments with great potential to improve cognitive function in poststroke patients. However, further improvements are needed in the effectiveness of a single non-invasive brain stimulation technique for cognitive rehabilitation. This study protocol aims to investigate the effect and neural mechanism of the combination of tDCS and taVNS on cognitive function in patients who had a stroke. METHODS AND ANALYSIS: In this single-centre, prospective, parallel, randomised controlled trial, a total of 66 patients with poststroke cognitive impairment will be recruited and randomly assigned (1:1:1) to the tDCS group, the taVNS group and the combination of tDCS and taVNS group. Each group will receive 30 min of treatment daily, five times weekly for 3 weeks. Primary clinical outcome is the Montreal Cognitive Assessment. Secondary clinical outcomes include the Mini-Mental State Examination, Stroop Colour Word Test, Trail Marking Test, Symbol Digit Modalities Test and Modified Barthel Index. All clinical outcomes, functional MRI and diffusion tensor imaging will be measured at preintervention and postintervention. ETHICS AND DISSEMINATION: The trial has been approved by the Ethics Committee of the First Affiliated Hospital of Yangtze University (approval no: KY202390). The results will be submitted for publication in peer-reviewed journals or at scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300076632.


Assuntos
Disfunção Cognitiva , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Estimulação do Nervo Vago , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Imagem de Tensor de Difusão , Estudos Prospectivos , Estimulação do Nervo Vago/métodos , Qualidade de Vida , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/terapia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
J Dent Sci ; 19(2): 1012-1020, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38618072

RESUMO

Background/purpose: The relationship between Vitamin D (VD) and periodontitis in patients with metabolic syndrome (MetS) was unclear. This study was to investigate the relationship between VD and periodontitis in MetS patients. Materials and methods: This cross-sectional study collected the data of 2165 MetS patients from the National Health and Nutrition Examination Survey (NHANES). The weighted univariate and multivariable Logistic regression models were applied to identify covariates and evaluate the association between 25-hydroxy vitamin D (25(OH)D) [25(OH)D]2 + 25(OH)D3 and periodontitis in patients. Odds ratio (OR) [95% confidence interval (CI)] was effect size. Subgroup analysis was performed in people with or without diabetes, dyslipidemia, hypertension, cardiovascular disease (CVD) and central obesity groups. Results: In the unadjusted model, compared with patients with 25(OH)D2 + 25(OH)D3 < 50 nmol/L, those with 25(OH)D2 + 25(OH)D3 ≥ 50 nmol/L might be associated with decreased risk of periodontitis in MetS patients (OR = 0.70, 95% CI: 0.57-0.85). After adjusting for confounders including age, gender, race, education, poverty income ratio (PIR), smoking, diabetes, VD intake and supplement and number of missing teeth, 25(OH)D2 + 25(OH)D3 ≥ 50 nmol/L was correlated with reduced risk of periodontitis in MetS patients (OR = 0.76, 95% CI: 0.60-0.97). Subgroup analysis revealed that in patients with CVD (OR = 0.60, 95% CI: 0.37-0.98), dyslipidemia (OR = 0.75, 95% CI: 0.57-0.97), and patients with central obesity (OR = 0.73, 95% CI: 0.57-0.95), decreased risk of periodontitis was identified in 25(OH)D2 + 25(OH)D3 ≥ 50 nmol/L. Conclusion: VD was associated with the risk of periodontitis in patients with MetS, which suggest the importance of VD supplement in patients with MetS and provide a reference for the management of periodontitis in patients with MetS.

3.
Zhongguo Zhong Yao Za Zhi ; 49(6): 1540-1548, 2024 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38621937

RESUMO

This study aims to reveal the effects of maltodextrin(MD) on the water adsorption and thermodynamic properties of Codonopsis Radix(DS) spray-dried powder by determining the moisture and energy changes of the powder in the process of moisture absorption. The static weighing method was used to obtain the isothermal water adsorption data of the spray-dried powder in 6 saturated salt solutions(KAc, MgCl_2·6H_2O, K_2CO_3, NaBr, NaCl, and KCl) at 3 temperatures(25, 35, and 45 ℃). Six models were used for fitting of the water adsorption process, and the most suitable model was selected based on the model performance. Furthermore, the corresponding net equivalent adsorption heat and differential entropy were calculated, and the adsorption entropy change was integrated. The linear relationship between net equivalent adsorption heat and differential entropy was drawn based on the entropy-enthalpy complementarity theory. The results showed that the water adsorption properties of DS and DS-MD spray-dried powder followed the type Ⅲ isotherm and was well fitted by the GAB model. The monolayer water content M_0 decreased with the increase in temperature. At the same temperature, the M_0 of DS spray-dried powder decreased after the addition of MD. The net equivalent adsorption heat and differential entropy of DS and DS-MD spray-dried powder decreased with the increase in water content, which presented a linear relationship. The addition of MD decreased the water activity corresponding to the lowest integral adsorption entropy of the powder, and the system became more stable. The results indicated that the spray-dried powder became more stable after the addition of MD.

4.
Methods Mol Biol ; 2782: 89-95, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38622394

RESUMO

Communication among neutrophils plays critical roles during various phases of inflammatory responses, with clinical relevance to both acute and chronic inflammatory diseases. Despite its significance, underlying mechanisms are not well understood, due to the lack of an effective in vitro system to properly address this important question. Here we report a robust in vitro method to culture primary murine neutrophils derived from bone marrow, amenable for well-controlled studies of both neutrophil activation and intercellular communication among co-cultured neutrophils. This protocol can generate primary neutrophils with high purity and survival for an extended culture period, suitable for further phenotypic and functional analyses.

5.
J Nanobiotechnology ; 22(1): 181, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622641

RESUMO

Periodontitis is an inflammatory disease induced by the complex interactions between the host immune system and the microbiota of dental plaque. Oxidative stress and the inflammatory microenvironment resulting from periodontitis are among the primary factors contributing to the progression of the disease. Additionally, the presence of dental plaque microbiota plays a significant role in affecting the condition. Consequently, treatment strategies for periodontitis should be multi-faceted. In this study, a reactive oxygen species (ROS)-responsive drug delivery system was developed by structurally modifying hyaluronic acid (HA) with phenylboronic acid pinacol ester (PBAP). Curcumin (CUR) was encapsulated in this drug delivery system to form curcumin-loaded nanoparticles (HA@CUR NPs). The release results indicate that CUR can be rapidly released in a ROS environment to reach the concentration required for treatment. In terms of uptake, HA can effectively enhance cellular uptake of NPs because it specifically recognizes CD44 expressed by normal cells. Moreover, HA@CUR NPs not only retained the antimicrobial efficacy of CUR, but also exhibited more pronounced anti-inflammatory and anti-oxidative stress functions both in vivo and in vitro. This provides a good potential drug delivery system for the treatment of periodontitis, and could offer valuable insights for dental therapeutics targeting periodontal diseases.

6.
BMC Musculoskelet Disord ; 25(1): 262, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570760

RESUMO

BACKGROUND: Radiculopathy of the lower limb after acute osteoporotic vertebral fractures (OVFs) in the lower lumbar spine is uncommon in geriatric patients. Moreover, surgical intervention is generally recommended in patients who are irresponsive to conservative treatment. Determining an optimum surgical strategy is challenging considering the poor general condition of this population. Thus, herein, we established an algorithm for surgically managing this clinical scenario, hoping to provide a reference for making a surgical decision. METHODS: We retrospectively studied patients who suffered from new-onset radiculopathy of the lower limb after acute single-level OVFs in the lower lumbar spine and eventually underwent surgical intervention at our department. Information on the demographics, bone quality, AO spine classification of the vertebral fracture, pre-existing degenerative changes, including foraminal stenosis and lumbar disc herniation, and surgical intervention type was collected. Additionally, clinical outcomes, including preoperative and postoperative visual analog scale (VAS) scores for back and leg pain, Oswestry disability index (ODI), and MacNab criterion for response to surgery, were evaluated. RESULTS: From September 2019 to December 2021, a total of 22 patients with a mean age of 68.59 ± 9.74 years were analyzed. The most involved vertebra was L5 (54.5%), followed by L4 (27.3%) and L3 (18.2%). Among the 22 patients, 15 (68.2%) were diagnosed with the A1 type fracture of AO classification, and among them, 11 (73.3%) were characterized by the collapse of the inferior end plate (IEP). Three patients (13.6%) suffered from A2-type fractures, whereas four patients (18.2%) suffered from A3-type fractures. Pre-existing degenerative changes were observed in 12 patients (54.5%) of the patients. A total of 16 patients (72.7%) were treated by percutaneous kyphoplasty (PKP). Additionally, three patients underwent posterior instrumentation and fusion, two patients underwent a secondary endoscopic foraminoplasty, and one patient underwent a secondary radiofrequency ablation. The mean follow-up period was 17.42 ± 9.62 months. The mean VAS scores for leg and back pain and ODI decreased significantly after the surgery (P < 0.05). The total satisfaction rate at the last follow-up was 90.9% per the Macnab criterion. CONCLUSION: Patients with OVFs in the IEP are predisposed to suffer from radiculopathy of the lower limb. PKP alone or in combination with other minimally invasive surgical strategies is safe and effective in treating stable fractures. Additionally, aggressive surgical intervention should be considered in patients with unstable fractures or severe foraminal encroachment.


Assuntos
Fraturas por Compressão , Cifoplastia , Fraturas por Osteoporose , Radiculopatia , Fraturas da Coluna Vertebral , Humanos , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Fraturas da Coluna Vertebral/complicações , Fraturas da Coluna Vertebral/diagnóstico por imagem , Radiculopatia/diagnóstico por imagem , Radiculopatia/etiologia , Radiculopatia/cirurgia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Vértebras Lombares/lesões , Perna (Membro) , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/cirurgia , Resultado do Tratamento , Fraturas por Compressão/cirurgia
7.
Front Cell Infect Microbiol ; 14: 1308742, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38558852

RESUMO

Background: Growing evidence has shown that gut microbiome composition is associated with Biliary tract cancer (BTC), but the causality remains unknown. This study aimed to explore the causal relationship between gut microbiota and BTC, conduct an appraisal of the gut microbiome's utility in facilitating the early diagnosis of BTC. Methods: We acquired the summary data for Genome-wide Association Studies (GWAS) pertaining to BTC (418 cases and 159,201 controls) from the Biobank Japan (BBJ) database. Additionally, the GWAS summary data relevant to gut microbiota (N = 18,340) were sourced from the MiBioGen consortium. The primary methodology employed for the analysis consisted of Inverse Variance Weighting (IVW). Evaluations for sensitivity were carried out through the utilization of multiple statistical techniques, encompassing Cochrane's Q test, the MR-Egger intercept evaluation, the global test of MR-PRESSO, and a leave-one-out methodological analysis. Ultimately, a reverse Mendelian Randomization analysis was conducted to assess the potential for reciprocal causality. Results: The outcomes derived from IVW substantiated that the presence of Family Streptococcaceae (OR = 0.44, P = 0.034), Family Veillonellaceae (OR = 0.46, P = 0.018), and Genus Dorea (OR = 0.29, P = 0.041) exerted a protective influence against BTC. Conversely, Class Lentisphaeria (OR = 2.21, P = 0.017), Genus Lachnospiraceae FCS020 Group (OR = 2.30, P = 0.013), and Order Victivallales (OR = 2.21, P = 0.017) were associated with an adverse impact. To assess any reverse causal effect, we used BTC as the exposure and the gut microbiota as the outcome, and this analysis revealed associations between BTC and five different types of gut microbiota. The sensitivity analysis disclosed an absence of empirical indicators for either heterogeneity or pleiotropy. Conclusion: This investigation represents the inaugural identification of indicative data supporting either beneficial or detrimental causal relationships between gut microbiota and the risk of BTC, as determined through the utilization of MR methodologies. These outcomes could hold significance for the formulation of individualized therapeutic strategies aimed at BTC prevention and survival enhancement.


Assuntos
Neoplasias do Sistema Biliar , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Neoplasias do Sistema Biliar/genética , Causalidade
8.
Front Med (Lausanne) ; 11: 1377926, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562376

RESUMO

Background: The protective efficacy of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination against the new-onset gastrointestinal (GI) symptoms following COVID-19 infection is critical among patients with inflammatory bowel disease (IBD); however, the optimal protective vaccine dose remains unknown. Therefore, this study aimed to clarify whether there is a correlation between SARS-CoV-2 vaccinations and GI symptoms following Omicron infection in patients with IBD. Methods: We conducted a multicenter cross-sectional study of IBD patients among three tertiary hospitals in eastern China. Professional physicians collected all data using online questionnaires. The patients were stratified into four groups: patients who were unvaccinated and patients who received one, two, or three vaccination doses. The primary outcome was the presence of any new-onset GI symptoms after SARS-CoV-2 infection before a negative SARS-CoV-2 nucleic acid test or a negative self-testing for antigens. Results: In total, 536 patients with IBD (175 unvaccinated, 31 vaccinated, 166 vaccinated with two doses, and 164 vaccinated with three doses) reported having COVID-19 infection. Compared with the unvaccinated, the three vaccination doses group was associated with reduced GI symptoms after infection (adjusted odds ratio = 0.56, 95% confidence interval 0.34-0.90, P < 0.05). Reduced diarrhea (adjusted odds ratio = 0.54, 95% confidence interval 0.31-0.92, P < 0.05) and nausea or vomiting (adjusted odds ratio = 0.45, 95% confidence interval 0.21-0.92, P < 0.05) were observed in the three vaccination doses group compared with the unvaccinated group. Conclusions: In conclusion, in the 536 patients with IBD who reported COVID-19 infection, we found that the three vaccination doses, but not the one or two doses group, were associated with reduced GI symptoms after infection compared with the unvaccinated group.

9.
J Agric Food Chem ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598779

RESUMO

The microbial consortium FA12 that can release ferulic acid (FA) by fermenting distiller's grains was screened from Daqu. Taibaiella, Comamonadaceae, and Ochrobacum were highly abundant in FA12 by 16S rRNA gene sequencing. In the process of long-term acclimation with distiller's grains as a medium, the biomass of FA12 remained stable, and the pH value of fermentation liquid was also relatively stable. Meanwhile, the activities of cellulase, xylanase, and feruloyl esterase secreted by FA12 were stable in the ranges of 0.2350-0.4470, 0.1917-0.3078, and 0.1103-0.1595 U/mL, respectively, and the release of FA could reach 133.77 µg/g. It is proven that the microbial consortium has good genetic stability. In addition, the structural changes of lignocellulose in distiller's grains before and after fermentation were analyzed by scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR), and the changes of distiller's grains weight and lignocellulose content before and after fermentation were also detected. These results all confirmed that FA12 had the function of degrading distiller's grains. In this study, we explored a method to use microbial communities to release FA from distiller's grains and degrade lignocellulose in the waste, which opened up a new way for the application of the high value of lost waste.

10.
Talanta ; 274: 126021, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38569370

RESUMO

α-hemolysin (Hla), a toxin secreted by Staphylococcus aureus (S. aureus), has been proved to be involved in the occurrence and aggravation of food poisoning. Hence, it is quite essential to establish its rapid detection methods to guarantee food safety. Sandwich ELISA based on nanobody is well known to be viable for toxins, but there is absence of nanobody against Hla, let alone a pair for it. Therefore, in this paper, we screened specific nanobodies by bio-panning and obtained the optimal nanobody pair for sandwich ELISA firstly. Then, RANbody, a novel nanobody owning both recognition and catalytic capability, is generated in a single step and at low cost through molecular recombination technology. Subsequently, sandwich ELISA was developed to detect Hla based on the nanobody and RANbody, that not only eliminated the use of secondary antibodies and animal-derived antibody, but also reduced detection time and cost, compared with traditional sandwich ELISA. Lastly, the performance has been evaluated, especially for specificity which showed no response to other hemolysins and a low limit of detection of 10 ng/mL. Besides, the proposed sandwich ELISA exhibits favorable feasibility and was successfully employed for the detection of Hla in milk and pork samples.

12.
Shanghai Kou Qiang Yi Xue ; 33(1): 54-58, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38583025

RESUMO

PURPOSE: To compare the forming ability of four kinds of nickel-titanium instrument preparation resin for simulated curved root canal. METHODS: A total of 40 single bend resin simulated root canals were randomly divided into 4 groups with 10 in each group. Four kinds of nickel-titanium instruments (ProTaper, HyFlex EDM, WaveOne Gold and Reciproc Blue) were used for root canal preparation, and divided into group A, group B, group C and group D. The preparation time of the four groups was compared, the root canal images before and after preparation were analyzed by computer image analysis software, and the changes of the preparation time, curvature and curvature radius of the four groups were recorded. With the root tip as the center of the circle, the radius of 1-10 mm was selected as concentric circle arcs. The detection points were overlapping root canal intersection points. The resin removal amount and center positioning force of the inner and outer walls of the root canal at different detection points were recorded. Statistical analysis was performed with SPSS 20.0 software package. RESULTS: The root canal preparation time in group A was significant longer than that in group B, C and D(P<0.05), but there was no significant difference in the curvature and curvature radius of the root canal among the four groups (P>0.05). The removal amount of resin from the root canal wall in group C was significant lower than that in group A, B and D (P<0.05) when the distance from the detection point to the apical foramina was 5, 6, 8, 9 and 10 mm, respectively. The removal amount of resin from the outer wall of the root canal in group C was significant lower than that in group A, B and D (P<0.05) when the distance from the detection point to the apical foramina was 5, 6, 7, 9 and 10 mm, respectively. The root tip offset of group A from the detection point to the apical hole of 1, 2, 3, 4, 6, 7, 8, 9 and 10 mm was significant greater than that of group B, C and D(P<0.05). CONCLUSIONS: Among the four instruments, ProTaper has the largest apical deviation, HyFlex EDM, WaveOne Gold and Reciproc Blue have better ability of root canal forming.


Assuntos
Cavidade Pulpar , Titânio , Níquel , Instrumentos Odontológicos , Preparo de Canal Radicular/métodos , Desenho de Equipamento
13.
Cancer Lett ; : 216857, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38583648

RESUMO

The considerable death rates and lack of symptoms in early stages of gastric cancer (GC) make it a major health problem worldwide. One of the most prominent risk factors is infection with Helicobacter pylori. Many biological processes, including those linked with cell death, are disrupted in GC. The cellular "self-digestion" mechanism necessary for regular balance maintenance, autophagy, is at the center of this disturbance. Misregulation of autophagy, however, plays a role in the development of GC. In this review, we will examine how autophagy interacts with other cell death processes, such as apoptosis and ferroptosis, and how it affects the progression of GC. In addition to wonderful its role in the epithelial-mesenchymal transition, it is engaged in GC metastasis. The role of autophagy in GC in promoting drug resistance stands out. There is growing interest in modulating autophagy for GC treatment, with research focusing on natural compounds, small-molecule inhibitors, and nanoparticles. These approaches could lead to breakthroughs in GC therapy, offering new hope in the fight against this challenging disease.

14.
Liver Int ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38606676

RESUMO

BACKGROUND AND PURPOSE: Liver fibrosis is a wound-healing reaction which is the main cause of chronic liver diseases worldwide. The activated hepatic stellate cell (aHSC) is the main driving factor in the development of liver fibrosis. Inhibiting autophagy of aHSC can prevent the progression of liver fibrosis, but inhibiting autophagy of other liver cells has opposite effects. Hence, targeted inhibition of autophagy in aHSC is quite necessary for the treatment of liver fibrosis, which prompts us to explore the targeted delivery system of small molecule autophagy inhibitor hydroxychloroquine (HCQ) that can target aHSC and alleviate the liver fibrosis. METHODS: The delivery system of HCQ@retinol-liposome nanoparticles (HCQ@ROL-LNPs) targeting aHSC was constructed by the film dispersion and pH-gradient method. TGF-ß-induced HSC activation and thioacetamide (TAA)-induced liver fibrosis mice model were established, and the targeting ability and therapeutic effect of HCQ@ROL-LNPs in liver fibrosis were studied subsequently in vitro and in vivo. RESULTS: HCQ@ROL-LNPs have good homogeneity and stability. They inhibited the autophagy of aHSC selectively by HCQ and reduced the deposition of extracellular matrix (ECM) and the damage to other liver cells. Compared with the free HCQ and HCQ@LNPs, HCQ@ROL-LNPs had good targeting ability, showing enhanced therapeutic effect and low toxicity to other organs. CONCLUSION: Construction of HCQ@ROL-LNPs delivery system lays a theoretical and experimental foundation for the treatment of liver fibrosis and promotes the development of clinical therapeutic drugs for liver diseases.

15.
J Nanobiotechnology ; 22(1): 168, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38610015

RESUMO

BACKGROUND: Oral cancer is the most common malignant tumor of the head and neck, and 90% of cases are oral squamous cell carcinoma (OSCC). Chemotherapy is an important component of comprehensive treatment for OSCC. However, the clinical treatment effect of chemotherapy drugs, such as doxorubicin (DOX), is limited due to the lack of tumor targeting and rapid clearance by the immune system. Thus, based on the tumor-targeting and immune evasion abilities of macrophages, macrophage membrane-encapsulated poly(methyl vinyl ether alt maleic anhydride)-phenylboronic acid-doxorubicin nanoparticles (MM@PMVEMA-PBA-DOX NPs), briefly as MM@DOX NPs, were designed to target OSCC. The boronate ester bonds between PBA and DOX responded to the low pH value in the tumor microenvironment, selectively releasing the loaded DOX. RESULTS: The results showed that MM@DOX NPs exhibited uniform particle size and typical core-shell structure. As the pH decreased from 7.4 to 5.5, drug release increased from 14 to 21%. The in vitro targeting ability, immune evasion ability, and cytotoxicity of MM@DOX NPs were verified in HN6 and SCC15 cell lines. Compared to free DOX, flow cytometry and fluorescence images demonstrated higher uptake of MM@DOX NPs by tumor cells and lower uptake by macrophages. Cell toxicity and live/dead staining experiments showed that MM@DOX NPs exhibited stronger in vitro antitumor effects than free DOX. The targeting and therapeutic effects were further confirmed in vivo. Based on in vivo biodistribution of the nanoparticles, the accumulation of MM@DOX NPs at the tumor site was increased. The pharmacokinetic results demonstrated a longer half-life of 9.26 h for MM@DOX NPs compared to 1.94 h for free DOX. Moreover, MM@DOX NPs exhibited stronger tumor suppression effects in HN6 tumor-bearing mice and good biocompatibility. CONCLUSIONS: Therefore, MM@DOX NPs is a safe and efficient therapeutic platform for OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Animais , Camundongos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço , Neoplasias Bucais/tratamento farmacológico , Distribuição Tecidual , Macrófagos , Doxorrubicina/farmacologia , Concentração de Íons de Hidrogênio , Microambiente Tumoral
16.
Orphanet J Rare Dis ; 19(1): 159, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38610036

RESUMO

BACKGROUND: Clinicians traditionally aim to identify a singular explanation for the clinical presentation of a patient; however, in some cases, the diagnosis may remain elusive or fail to comprehensively explain the clinical findings. In recent years, advancements in next-generation sequencing, including whole-exome sequencing, have led to the incidental identification of dual diagnoses in patients. Herein we present the cases of five pediatric patients diagnosed with dual rare genetic diseases. Their natural history and diagnostic process were explored, and lessons learned from utilizing next-generation diagnostic technologies have been reported. RESULTS: Five pediatric cases (3 boys, 2 girls) with dual diagnoses were reported. The age at diagnosis was from 3 months to 10 years. The main clinical presentations were psychomotor retardation and increased muscular tension, some accompanied with liver dysfunction, abnormal appearance, precocious puberty, dorsiflexion restriction and varus of both feet, etc. After whole-exome sequencing, nine diseases were confirmed in these patients: Angelman syndrome and Krabbe disease in case 1, Citrin deficiency and Kabuki syndrome in case 2, Homocysteinemia type 2 and Copy number variant in case 3, Isolated methylmalonic acidemia and Niemann-Pick disease type B in case 4, Isolated methylmalonic acidemia and 21-hydroxylase deficiency in case 5. Fifteen gene mutations and 2 CNVs were identified. Four novel mutations were observed, including c.15292de1A in KMT2D, c.159_164inv and c.1427G > A in SLC25A13, and c.591 C > G in MTHFR. CONCLUSIONS: Our findings underscore the importance of clinicians being vigilant about the significance of historical and physical examination. Comprehensive clinical experience is crucial for identifying atypical clinical features, particularly in cases involving dual rare genetic diseases.


Assuntos
Anormalidades Múltiplas , Erros Inatos do Metabolismo dos Aminoácidos , Síndrome de Angelman , Citrulinemia , Masculino , Feminino , Humanos , Criança , Proteínas de Transporte da Membrana Mitocondrial
17.
J Anim Sci ; 1022024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38563227

RESUMO

The liver plays a critical role in metabolic activity and is the body's first immune barrier, and maintaining liver health is particularly important for poultry production. MicroRNAs (miRNAs) are involved in a wide range of biological activities due to their capacity as posttranscriptional regulatory elements. A growing body of research indicates that miR-21-5p plays a vital role as a modulator of liver metabolism in various species. However, the effect of miR-21-5p on the chicken liver is unclear. In the current study, we discovered that the fatty liver had high levels of miR-21-5p. Then the qPCR, Western blot, flow cytometry, enzyme-linked immunosorbent assay, dual-luciferase, and immunofluorescence assays were, respectively, used to determine the impact of miR-21-5p in the chicken liver, and it turned out that miR-21-5p enhanced lipogenesis, oxidative stress, and inflammatory responses, which ultimately induced hepatocyte apoptosis. Mechanically, we verified that miR-21-5p can directly target nuclear factor I B (NFIB) and kruppel-like factor 3 (KLF3). Furthermore, our experiments revealed that the suppression of NFIB promoted apoptosis and inflammation, and the KLF3 inhibitor accelerated lipogenesis and enhanced oxidative stress. Furthermore, the cotransfection results suggest that the PI3K/AKT pathway is also involved in the process of miRNA-21-5p-mediate liver metabolism regulation. In summary, our study demonstrated that miRNA-21-5p plays a role in hepatocyte lipogenesis, oxidative stress, inflammation, and apoptosis, via targeting NFIB and KLF3 to suppress the PI3K/AKT signal pathway in chicken.


miR-21-5p is a typical noncoding RNA that could inhibit messenger RNA expression by targeting the 3ʹ-untranslated region to participate in fatty liver-related disease formation and progression. We demonstrated that miRNA-21-5p plays a role in hepatocyte lipogenesis, oxidative stress, inflammation, and apoptosis, via targeting nuclear factor I B and kruppel-like factor 3 to suppress the PI3K/AKT signal pathway in chicken. This research established the regulatory network mechanisms of miR-21-5p in chicken hepatic lipogenesis and fatty liver syndrome.


Assuntos
MicroRNAs , Proteínas Proto-Oncogênicas c-akt , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Transcrição NFI/metabolismo , Galinhas/genética , Galinhas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Lipogênese/genética , Transdução de Sinais , MicroRNAs/genética , MicroRNAs/metabolismo , Fígado/metabolismo , Apoptose , Inflamação/metabolismo , Inflamação/veterinária , Proliferação de Células
18.
Photodiagnosis Photodyn Ther ; : 104087, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38614271

RESUMO

Plantar wart is one of the most recalcitrant types of cutaneous warts with a high recurrence rate. Recalcitrant plantar warts are resistant to traditional treatments such as cryotherapy. Photodynamic therapy (PDT) is a modern, non-invasive method utilized to treat benign and malignant skin disorders. Several previous studies have reported the effective application of PDT treatment for plantar warts. We reported three cases of recalcitrant plantar warts successfully treated with PDT.

19.
Artigo em Inglês | MEDLINE | ID: mdl-38581365

RESUMO

Nitric oxide (NO) intervenes, that is, a potential treatment strategy, and has attracted wide attention in the field of tumor therapy. However, the therapeutic effect of NO is still poor, due to its short half-life and instability. Therapeutic concentration ranges of NO should be delivered to the target tissue sites, cell, and even subcellular organelles and to control NO generation. Mitochondria have been considered a major target in cancer therapy for their essential roles in cancer cell metabolism and apoptosis. In this study, mesoporous silicon-coated gold nanorods encapsulated with a mitochondria targeted and the thermosensitive lipid layer (AuNR@MSN-lipid-DOX) served as the carrier to load NO prodrug (BNN6) to build the near-infrared-triggered synergetic photothermal NO-chemotherapy platform (AuNR@MSN(BNN6)-lipid-DOX). The core of AuNR@MSN exhibited excellent photothermal conversion capability and high loading efficiency in terms of BNN6, reaching a high value of 220 mg/g (w/w), which achieved near-infrared-triggered precise release of NO. The outer biocompatible lipid layer, comprising thermosensitive phospholipid DPPC and mitochondrial-targeted DSPE-PEG2000-DOX, guided the whole nanoparticle to the mitochondria of 4T1 cells observed through confocal microscopy. In the mitochondria, the nanoparticles increased the local temperature over 42 °C under NIR irradiation, and a high NO concentration from BNN6 detected by the NO probe and DSPE-PEG2000-DOX significantly inhibited 4T1 cancer cells in vitro and in vivo under the synergetic photothermal therapy (PTT)-NO therapy-chemotherapy modes. The built NIR-triggered combination therapy nanoplatform can serve as a strategy for multimodal collaboration.

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